Liver cancer 2016: From immunotherapy to gene therapy and beyond

December 24, 2015
| by Veronique de Turenne

By the end of 2016, treatment for liver cancer could look much different than it does now.

Progress in the evolving field of immunotherapy and the emerging field of viral-based gene therapy herald a promising new era in the field of liver cancer. These research advances, along with new technologies that allow for less invasive surgeries, offer a bright outlook for the year ahead.

Here, we speak with two of City of Hope’s liver cancer specialists, Yuman Fong, M.D., chair of the Department of Surgery, and Vincent Chung, M.D., associate clinical professor in the Department of Medical Oncology & Therapeutics Research. They answer five questions about what they expect to see in liver cancer treatment and research in the coming year.

Fong is an internationally acclaimed expert in cancer of the liver, as well as of the pancreas, bile ducts and gallbladder. He is renowned for his use of genetically modified viruses to combat malignant disease. A pioneer in both the operating room and the research lab, Fong is the author of more than 600 peer-reviewed articles and 11 textbooks.

Chung, who was voted one of “America's Top Doctors” by Castle Connolly in 2013, specializes in cancers of the digestive system. These include cancer of the liver, pancreas, gallbladder stomach and bowel. He oversees a number of clinical trials at City of Hope, which evaluate new drugs to treat advanced solid tumors.

1. What treatment advances do you expect for liver cancer patients in 2016?

“Viral therapy is going to be really hot in the next six to 12 months,” Fong said, referring to the use of genetically modified viruses, which exploit mutations that exist in cancer cells but not in normal cells.

“Fifteen years ago, when I began working with viral therapy, it was thought to be so radical,” Fong said. “Now, it’s a whole new field that is exploding, and we at City of Hope have done as much as anyone to advance it.”

Chung foresees similar good news in the field of immunotherapy.

“Immunotherapy is an extremely exciting development in cancer care,” Chung said. “Earlier this year at the American Society of Clinical Oncology meeting, we heard many presentations about checkpoint inhibitors such as nivolumab (Opdivo) or pembrolizumab (Keytuda) having clinical responses in solid tumors.”

For patients whose tumors can be removed, Fong is enthusiastic about the precision and minimal impact of robotic surgery. Also increasingly valuable is a procedure known as ablation, in which small tumors are destroyed with electricity, radio waves, microwaves or by freezing, Fong said.

“That’s one of the neatest things happening in field right now – the ability to do work through these minimally invasive ways,” Fong said.

2. How significant is that?

Anything that reduces recovery time and limits a patient’s pain and discomfort is a boon, Fong said of the growing trend toward robotic surgery and ablation.

“Many of our patients at City of Hope can have surgery and leave the hospital in one or two or three days,” Fong said. “That allows them to get back home and resume a normal life.”

As for the new directions in virotherapy and immunotherapy, Fong and Chung agree that these fields offer new hope through cancer treatment that is tailored to each individual patient’s genetic profile, and is specific to their type of cancer.

“We are seeing the immune system developing memory, which then reactivates to kill future cancer cells,” Chung said, referring to the ongoing positive response in patients successfully treated with immunotherapy. “We still have a lot to learn about the immune system and how to harness the power, but this is an exciting start.”

“We are making viruses that are cancer killers,” Fong said. “We are arming them with things we know don’t hurt the human being.”

Immunotherapy, which enlists each patient’s own immune system to fight cancer, will achieve the same goals – killing cancer cells without harming healthy cells, Fong and Chung said.

4. What research progress do you expect in 2016?

“We have a number of viral therapy trials coming to maturity that we will be reporting on in the next six to 12 months,” Fong said. “We are exploring the idea that you inject a virus into a patient, that virus finds the cancer cell, and then infects and kills it.”

By using viral vectors, Fong foresees therapies such as sending a specialized protein to shut down the growth of blood vessels within a tumor, which starves it to death. Another avenue of study is the use of a specialized protein that is toxic to the cancer cell and kills it, but causes no harm to healthy cells.

5. Overall, where is the field of liver cancer treatment and research moving?

In addition to the fields of viral therapy and immunotherapy, researchers are working on methods of early detection, which is crucial to successful treatment of liver cancer, Fong said.

“Several new blood tests are being studied to see if they can detect liver cancer earlier than using by using AFP and ultrasound,” Fong said. A high blood level of AFP, or alpha-fetoprotein, is often present in people with liver cancer.

“One new test that is promising is called DKK1,” Fong said.

The new test measures blood levels of a biomarker known as Dickkopf-1, or DKK1. It has shown good results in identifying the most common type of liver cancer, known as hepatocellular carcinoma (HCC).

In HCC, which is linked to chronic liver disease, AFP levels may not become detectably high until a patient’s cancer has advanced. The DKK1 test, however, has shown promise in detecting liver cancer in its earlier stage, when it is more treatable, Fong said.

A study into the effect of the immunotherapy drug Opdivo (nivolumab) in HCC has yielded encouraging results that merit further investigation, Chung said.

“Researchers reported a response rate of 19 percent, which is much better than the 2 percent response rate with the FDA-approved drug sorafenib (Nexavar),” Chung said. “The side effect profile was much better as well, which gives hope to patients of having an improved quality of life while fighting the cancer.”